Unusual chemo- and stereo-selectivities in the reactions of 1,2-dichlorocyclopropenes with nitrile oxides

摘要

J. CHEM. soc. PERKIN TRANS. 1 1993 Unusual Chemo- and Stereo-selectivities in the Reactions of 12-Dic h Iorocyclopro penes with NitriIe Oxides Mark S. Baird,**8 Xiaoming LL8 Juma'a R. Al Dulayymi,8 Alexander 1. Kurdjukovb and Valery A. Pavlovb Department of Chemistry, University of Wales, Bangor, Gwynedd, LL57 2UW UK Department of Organic Chemistry, Kazan State Technological University, Kazan, Russia 1,2-Dichloro-3,3-dimethylcyclopropene reacts with a number of nitrile oxides to produce oxazines in moderate to good yield in a reaction which apparently involves an unusual formal 3-centre plus 3-centre cycloaddition of the dipole to an intermediate vinylcarbene. In contrast, 1,2-dichloro-3-chloromethyl-3-methylcyclopropene undergoes a dipolar cycloaddition to produce a 2-oxa-3-azabicyclo3.1 .O -hex-3-ene in which the 6-chloromethyl substituent occupies the endo-position.6H-1,2-Oxazines have been prepared by a number of routes, many of which involve the cyclisation of a four-atom unit with a two-atom unit, such as the cycloaddition of an alkenyl nitroso compound to an alkene to give a 4,s-dihydro compound,' or to an allene to give a 6-methylene-4,S-dihydro compound which may be isomerised, by treatment with base, to the 1,2-0xazine.~ There are few examples of the formation of the heterocycle by combination of two three-atom components to form the ring, although addition of sulfoxonium allylides to nitrile oxides does lead to 1,2-oxazines as minor products together with fur an^.^ We now report that reaction of a 1 ,2-dichloro-3,3-dialkylcyclo-propene with nitrile oxides leads to 1,2-oxazines in moderate to good yield.Treatment of la4 with the nitrile oxide 2at for 18 h at 20 "C in diethyl ether gave the oxazine 3a (65), m.p. 125-127 "C. ?I CI MeA-X CI la X=H 3 X=H b X=CI 4 X=CI a, R = 2,4,6-(Meuro;?0)3C6H2;b, R = 3,4-(MeO)amp;H3 c, R = 2-02NC,H4;d, R = C,H,; e, R = (PiO),PO The structure of 3a, the "C NMR of which included a signal at S 84 for C-6,$ was confirmed by an X-ray crystal structure determination and is given in Fig. 1.9 This reaction is quite different from the addition of nitrile oxides to simple alkyl- and aryl-cyclopropenes which has been reported to lead to 2-oxa-3- azabicyclo3.1 .Ohex-Zenes in a typical dipolar addition to the strained alkene.' It is known that cyclopropenes such as la ring-open at ambient temperature to produce vinylcarbenes which may be trapped in a range of intermolecular reactions such as addition to alkenes, insertion into carbon-hydrogen bonds adjacent to oxygen and addition to carbon-phosphorus triple The formation of oxazines 3 could formally occur by addition of the singlet vinylcarbene 5 (X = H), which may be regarded as an ally1 cation orthogonal to an anion on C-1, to the 7 The nitrile oxide 2a was used as a crystalline solid.In the other cases, the compounds were prepared in situ by reaction of the corresponding chloro oxime with triethylamine in diethyl ether. Compound 3b showed 8" 7.1 (1 H, d, J 7), 7.05 (1 H, s), 6.85 (1 H, d, J 7), 3.85 (3 H, s), 3.84 (3 H, s), 1.5 (6 H, s); dC 155.9, 150.6, 148.7, 140.3, 124.3, 111.4, 110.5,80.2, 56.0,55.95 and23.7.0 Thanks are due to the SERC Crystallography service in Swansea for carrying out this structure determination. nitrile oxide, although it is not clear as yet whether this process occurs in a stepwise or concerted manner, e.g.: 6 The reaction is also successful with a range of other nitrile oxides 2b-eas shown in Table 1; in each case the spectrum included a signal at 6 80-84 for C-6. However, the related cyclopropenelb, which is also known to rearrange to a carbene 5 (X= Cl) at ambient temperature,' reacts with the nitrile oxides by an apparent direct dipolar cycloaddition to give the oxabicycles 6 rather than 4.7 These showed a characteristic signal for C-5 at S90-95, but no signal at 6 80-84.The stereo-chemistry of 6a was established by X-ray crystallography.sect; The reason for the difference in behaviour of the two cyclopropenes may lie in the kinetics of their ring-opening to carbenes; thus, it is known that the trapping of the carbene 5 (X = H) derived from la by alkenes occurs somewhat faster than the corres- ponding sequence from lb, probably reflecting a difference in the rates of ring-opening.' However, the formation of the more hindered endo-isomer may reflect a more subtle effect of the remote C-Cl bond in controlling the stereochemistry of the reaction at the n-bond of lb and/or in increasing the rate of cycloaddition relative to that for la.Further work is in progress to analyse the effect, which may be related to the high degree of stereocontrol of ring-opening of lb to the carbene 5 (X= Cl),' which has been explained in terms of electronic interactions in the transition state involving the orbitals of the chloromethyl group,8 and to n-facial selectivity observed in the additions of 7-methyknebicyclo2.2. llheptane derivatives induced by an enido-2-sub~tituent.~*~~It should be noted, however, that addition of e.g., nitrile oxides to the n-bond to 3-methyl-3- phenyl- and 3-cyano-3-methyl-cyclopropenealso occurs in a highly stereocontrolled manner. 'J' 7 See Experimental section for spectroscopic data for 6a. 2508 J. CHEM.SOC. PERKIN TRANS. 1 1993 Fig. 1 X-Ray crystallographic structure of 3a Table 1 Reactions of cyclopropenes (la) and (lb) with nitrile oxides Cyclopropene Nitrile oxide Product Yield () la 2a 3a 65 la 2b 3b 55 la 2c 3c 35 la 2d 3d 35 la 2e 3e 80 lb 2a 6a 65 lb 2b 6b 60 lb 26 6d 30 lb 2e 6e 45 Experimenta1 Reaction of 1,2-Dichloro-3-chloromethyl-3-methylcyclopro-pene 1b with 2,4,6-Trimethoxybenzonitrile Oxide 2a.-A solution of 1,1,2,2-tetrachloro-3-chloromethyl-3-methylcyclopropane (1.0 g, 4.12 mmol) in dry diethyl ether (10 an3)was stirred under argon and cooled in an ice-salt bath. Methyllithium (1.5 rnol dm-3; 3.29 cm3, 1.2 mol equiv.) was then added dropwise to it over 1min. After 10 min the mixture was quenched with water (10 cm3) whilst being cooled in an ice-bath.The aqueous phase was extracted with diethyl ether (3 x 5 cm3) and the combined extracts, containing 3-chloromethyl-3-methyl- 1 ,2-dichlorocy- clopropene, were dried (MgSO,). A solution of 2,4,6-trimethoxybenzonitrile oxide (0.86 g, 1.0 rnol equiv.) in dry diethyl ether (20 cm') was added to the above ethereal solution and the reaction mixture was then stored at 20deg;C for 24 h. Evaporation of the reaction mixture to dryness gave the crude product which was purified by column chromatography (10 :3, light petroleum-diethyl ether as eluent) on silica gel, to give white crystals of compound 6a (1.O g, 65), m.p. 118-120 "C (Found: C, 47.7; H, 4.3; N, 3.6.Calc. for C15Hl,Cl,N04: C, 47.30; H, 4.20; N, 3.68);6,6.10 (2 H, s), 3.80 (3 H, s), 3.75 (6 H,s),3.46(1H,d,J11.8),3.23(1H,d,J11.8)and1.6(3H,s);amp; 163.9s, 160.3s, 156.4, 1533, 97.4, 92.3, 90.9d, 65.4, 56.lq, 55.6q, 47.2s, 43.2t, 32.9 and 15.7; on running the 13C spectrum at -20 OC, the signal at 6 90.9 was split into two signals at 6 90.5 and 89.9. The presence of additional 13C signals is presumed to be caused by restricted rotation of the aryl-group. Reaction of 1,2-Dichloro-3,3-dimethylcyclopropenela with Benzonitrile Oxide 2d.-A solution of 3-bromo-l , 1,3-trichloro-2,2-dimethylcyclopropane (1.O g, 3.95 mmol) in dry diethyl ether (10 cm3) was stirred under argon and cooled to -78 "C. Methyllithium (1.5 mol dmP3; 2.9 an3, 1.1 mol equiv.) was added to the solution which was then kept -40 "C for 10 min.After being quenched with water (10 cm3)at -40 "C the mixture was extracted with diethyl ether (3 x 5 cm3) and the combined extracts, containing 3,3-dimethyl- 1,2-dichlorocyclo- propene, were dried (MgSO,) at -40 "C. A solution of benzo- hydroxamoyl chloride (0.62 g, 3.95 mmol) in dry diethyl ether (20 cm3) was stirred at 0 "C and treated with freshly distilled triethylamine (0.45 g, 1.0 mol equiv.), added in one portion. The mixture was then shaken continuously for 5 min while being cooled in an ice-bath. The two ethereal solutions were combined and kept at room temperature for 24 h. The mixture was washed with hydrochloric acid (10; 10 cm3) and water (3 x 10 an3),dried (MgS0,) and evaporated to dryness; the crude product was purified by column chromatography (1 0 :2, light petroleum-diethyl ether) on silica gel, to give white crys- tals of compound 3d (0.55 g, 5573, m.p.102-104 "C (Found: C, 56.7; H, 4.3; N, 5.9. Calc. for C12H,,Cl,NO: C, 56.25; H, 4.30; N, 54.7); 6, 8.02-7.95 (2 H, m), 7.48-7.45 (3 H, m) and 1.08 (6 H, s);~C 139.0, 134.1, 132.9, 130.3, 129.0, 128.6, 128.2, 125.6, 121.8, 79.6 and 23.1. References 1 For a recent example see T. Arnold, B.Orschel and H. U. Reissig, Angew. Chem., Int. Edn. Engl., 1992,31, 1084. 2 C. Unger, R. Zimmer, H. U. Reissig and E. U. Wuerthwien, Chem. Ber., 1991, 124,2279. 3 Y. Nakada, T. Hata, C. Tamura, T. Iwaoka, M. Kondo and J. Ide, Tetrahedron Lett., 1981,473.4 M. S. Baird and H. H. Hussain, Tetrahedron, 1989,45,6221. 5 I. G. Bolesov, A. V. Ignatchenko, N. V. Bovin, P. V. Prudchenko, L. S. Surmina, V. V. Plemenkov, P. V. Petrovskii, I. V. Romanov and I. I. Mel'nik, Zh. Org. Khim., 1990,26, 102; M. Nitta, S. Sogo and T. Nakayama, Chem. Lett., 1979, 1431; M. Nitta, S. Sogo and T. Nakayama, Heterocycles, 1980, 14, 136; J. Visser and P. Smael, Tetrahedron Lett., 1973, 1139; L. G. Zaitseva, L. A. Berkovich and I. G. Bolesov, Zh. Org. Khim., 1974,10, 1669; L. G. Zaitseva, 0.S. Chizhov and I. G. Bolesov, Zh. Org. Khim., 1975, 11, 1347. 6 H. Memmesheimer, J. R. A1 Dulayymi, M. S. Baird, T. Wettling and M. Regitz, Synlett., 1991,433. 7 J. R. A1Dulayymi, M. S. Bird and H. H. Hussain, Tetrahedron Lett., 1989, 2009; J. R. A1 Dulayymi, M. S. Baird and W. Clegg, Tetrahedron Lett., 1988,6149; J. R. A1 Dulayymi and M. S. Baird, Tetrahedron,1989,45,7601; J. R. Al Dulayymi, M. S. Baird and W. Clegg, J. Chem. SOC.,Perkin Trans. I, 1989, 1799. 8 M. S. Baird, J. R. A1 Dulayymi, H. S.Rzepa and V. Thoss, J. Chem. Soc., Chem. Commun., 1992,1323. 9 G. Mehta and F. A. Khan, J. Chem. Soc., Chem. Commun., 1991,18. 10 B. Halton, R. Boese and H. S. Rzepa, J. Chem. Soc.,Perkin Trans. I, 1992,447; H. B. Broughton, S. M. Green and H. S. Rzepa, J. Chem. Soc., Chem. Commun., 1992,998. 1 1 V. A. Pavlov, A. I. Kurdjukov, V. V. Plemenkov, R. R. Khaliullin and V. V. Moskva, Zh. Org. Khim., 1993,63,637. Paper 31053671 Received 7th September 1993